Human combinatorial autoantibodies and mouse monoclonal antibodies to PDC-E2 produce abnormal apical staining of salivary glands in patients with coexistent primary biliary cirrhosis and Sjögren's syndrome

Koichi Tsuneyama, Judith A Van de Water, Yasuni Nakanuma, Sanghoon Cha, Aftab Ansari, Ross Coppel, M. Eric Gershwin

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Abstract

An increase in the incidence of Sjögren's syndrome in patients with primary biliary cirrhosis has been noted. Indeed, primary biliary cirrhosis has been described as a ductal disease with involvement not only of the biliary tract but of epithelial ductal cells in other organs. We have previously reported the development of a panel of mouse monoclonal antibodies directed at PDC-E2, the major autoantigen of primary biliary cirrhosis. One such antibody, C355.1, but none of the other monoclonal antibodies, reacted not only with mitochondria but also with the apical region of biliary epithelium of patients with primary biliary cirrhosis but not in similar specimens from patients with other liver disease or normal human liver. In addition, we have reported the development of human combinatorial antibodies specific for PDC-E2; these reagents also reacted uniquely with the biliary epithelium of patients with primary biliary cirrhosis. In this paper, we have performed a similar study and have compared the staining of monoclonal antibody C355.1 and a human combinatorial antibody, SP4, with control monoclonal antibodies with respect to their reactivity of salivary glands in 9 patients with primary biliary cirrhosis associated with Sjögren's syndrome, 11 patients with Sjögren's syndrome alone and 7 control patients. Interestingly, the apical region of the salivary gland epithelial cells of approximately 50% of patients with coexisting primary biliary cirrhosis and Sjögren's syndrome had a staining pattern similar to that seen in primary biliary cirrhosis biliary epithelium. In contrast, we did not observe this reactivity in any patient with Sjögren's syndrome alone or in any control patient. These data suggest that similar mechanisms may explain the abnormal expression pattern of PDC-E2 or a cross-reacting molecule in the ductal tissue of patients with primary biliary cirrhosis.

Original languageEnglish (US)
Pages (from-to)893-898
Number of pages6
JournalHepatology
Volume20
Issue number4 I
StatePublished - Oct 1994

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Biliary Liver Cirrhosis
Salivary Glands
Autoantibodies
Monoclonal Antibodies
Staining and Labeling
Epithelium
Antibodies
Epithelial Cells
Autoantigens
Biliary Tract
Human Development
Liver Diseases
Mitochondria

ASJC Scopus subject areas

  • Hepatology

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Human combinatorial autoantibodies and mouse monoclonal antibodies to PDC-E2 produce abnormal apical staining of salivary glands in patients with coexistent primary biliary cirrhosis and Sjögren's syndrome. / Tsuneyama, Koichi; Van de Water, Judith A; Nakanuma, Yasuni; Cha, Sanghoon; Ansari, Aftab; Coppel, Ross; Gershwin, M. Eric.

In: Hepatology, Vol. 20, No. 4 I, 10.1994, p. 893-898.

Research output: Contribution to journalArticle

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title = "Human combinatorial autoantibodies and mouse monoclonal antibodies to PDC-E2 produce abnormal apical staining of salivary glands in patients with coexistent primary biliary cirrhosis and Sj{\"o}gren's syndrome",
abstract = "An increase in the incidence of Sj{\"o}gren's syndrome in patients with primary biliary cirrhosis has been noted. Indeed, primary biliary cirrhosis has been described as a ductal disease with involvement not only of the biliary tract but of epithelial ductal cells in other organs. We have previously reported the development of a panel of mouse monoclonal antibodies directed at PDC-E2, the major autoantigen of primary biliary cirrhosis. One such antibody, C355.1, but none of the other monoclonal antibodies, reacted not only with mitochondria but also with the apical region of biliary epithelium of patients with primary biliary cirrhosis but not in similar specimens from patients with other liver disease or normal human liver. In addition, we have reported the development of human combinatorial antibodies specific for PDC-E2; these reagents also reacted uniquely with the biliary epithelium of patients with primary biliary cirrhosis. In this paper, we have performed a similar study and have compared the staining of monoclonal antibody C355.1 and a human combinatorial antibody, SP4, with control monoclonal antibodies with respect to their reactivity of salivary glands in 9 patients with primary biliary cirrhosis associated with Sj{\"o}gren's syndrome, 11 patients with Sj{\"o}gren's syndrome alone and 7 control patients. Interestingly, the apical region of the salivary gland epithelial cells of approximately 50{\%} of patients with coexisting primary biliary cirrhosis and Sj{\"o}gren's syndrome had a staining pattern similar to that seen in primary biliary cirrhosis biliary epithelium. In contrast, we did not observe this reactivity in any patient with Sj{\"o}gren's syndrome alone or in any control patient. These data suggest that similar mechanisms may explain the abnormal expression pattern of PDC-E2 or a cross-reacting molecule in the ductal tissue of patients with primary biliary cirrhosis.",
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